Fig. 3

Mucosal immune system in the lower respiratory tract. Type II alveolar epithelial cells are susceptible to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. After infection, the secretion of pulmonary surfactant is inhibited, the composition of alveolar surface mucosa changes, and gas exchange is blocked. Monocytes in the blood vessels are the source of alveolar macrophages. Most alveolar macrophages are differentiated into the M1 type after being infected by SARS-CoV-2. SARS-CoV-2 engulfed by M1 type macrophages is more likely to get leaked and cause more serious infection. Additionally, macrophages in the pulmonary interstitium become activated after endocytosis of SARS-CoV-2, resulting in pulmonary fibrosis. Antibody-dependent enhancement can lead to more severe infections. SARS-CoV-2 spike protein binds to neutralizing antibodies, and the Fc segment of the antibodies easily binds to CD16 on the surface of the macrophages, enabling the macrophages to swallow SARS-CoV-2 and cause infection. In infected macrophages, inflammasomes form and initiate pyroptosis, while releasing cytokines and chemokines to trigger cytokine storms